HOUSTON—Cannabidiol (CBD) interacts significantly with clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine, researchers said at the 70th Annual Meeting of the American Epilepsy Society. The study results underscore the importance of monitoring levels of antiepileptic drugs (AEDs) during treatment with CBD. “In the future, these data will need to be correlated with reported side effects or laboratory abnormalities to determine whether they are clinically significant,” said Jerzy P. Szaflarski, MD, PhD, Director of the University of Alabama at Birmingham Epilepsy Center.
Dr. Szaflarski and colleagues monitored serum AED levels during active titration of pharmaceutical grade CBD in patients with refractory epilepsy who were enrolled in an open-label safety study. The study was intended to investigate CBD as a potential adjunctive therapy. As part of the study protocol, researchers checked serum AED levels frequently to identify interactions between CBD and AEDs. Based on previous data and anecdotal observations, Dr. Szaflarski and colleagues hypothesized that they would find interactions between CBD and clobazam and valproate.
Participants received an initial CBD dose of 5 mg/kg/day. The dose was increased by 5 mg/kg/day every two weeks, provided that tolerability was maintained, to a maximum of 50 mg/kg/day. Baseline AED levels were drawn, and AEDs were required to have been at a stable dose for one month before enrollment. The researchers obtained AED levels at almost all study visits during dose titration and maintenance. AED doses were adjusted at the investigators’ discretion if an adverse effect, laboratory abnormality, or drug level change was considered related to a potential interaction between CBD and the AED. The researchers frequently adjusted doses of clobazam and valproate because of complaints of sedation and alteration in liver function tests, respectively. At the time of Dr. Szaflarski’s analysis, 81 participants were enrolled in the study (39 adults and 42 children). There were sufficient data to analyze potential interactions between CBD and 19 AEDs.
The researchers found increases in serum levels of topiramate, rufinamide, and desmethylclobazam (an active metabolite of clobazam), and a decrease in levels of clobazam, with increasing CBD dose in the pediatric and adult arms. In addition, they noted significant increases in serum levels of zonisamide and eslicarbazepine with increasing CBD dose in the adult arm. Dr. Szaflarski and colleagues observed no significant interactions between CBD and the other AEDs investigated, which included valproate, levetiracetam, lacosamide, and perampanel.